Paclitaxel (PTX) and gemcitabine (GEM) are often used in combination due to the synergistic anticancer effects. PTX and GEM combination showed a synergistic effect to SKOV-3 cells at a molar ratio of 1 to 1 and in PTX ➔ GEM sequence. Liposomes were explored as a carrier of PTX and GEM combination. We optimized the drug loading in liposomes varying the preparation method and co-encapsulated PTX and GEM in a single liposome preparation maintaining the maximum loading efficiency of each drug. However, drug release kinetics from the co-loaded liposomes (LpPG) was suboptimal because of the detrimental effect of PTX on GEM-release control. Instead, a mixture of LpP and LpG, which were separately optimized according to the desired release kinetics, achieved a greater cytotoxic effect than LpPG, due to the attenuation of GEM release relative to PTX.

The 2017 FDA safety review regarding the CNS (central nervous system) side effects associated withthe systemic use of fluoroquinolones antibacterials (FQs) was the key motivation to carry out this work.The main objective of this study is to investigate lipophilicity and retention parameters of some selectedfluoroquinolones antibacterials (FQs) namely; levofloxacin (LEV), ofloxacin (OFL), gatifloxacin (GAT), nor-floxacin (NOR), sparfloxacin (SPA), ciprofloxacin (CIP) and lomefloxacin (LOM) using salting-out thinlayer chromatography (SOTLC). Statistically significant correlations between the chromatographically-obtained retention parameters and experimental log P values were found and expressed as quantitativestructure retention relationship (QSRR) equations. Principal component analysis was carried out toexplain the variation between chromatographic and both experimental and computed lipophilicityparameters. In another aspect of this study, a comparison between the chromatographically-determinedretention parameters (for five of the drugs under study) obtained using SOTLC (current study) and rel-ative lipophilicity (RM0) determined using a previously reported RP (reversed-phase)-TLC method wascarried out. Statistically significant correlation between the two methods was found, although RM0valuesobtained using SOTLC was lower than those reported using RP-TLC. Multiple linear regression analysiswas performed to predict MIC (minimum inhibitory concentration) and blood brain barrier (BBB) pene-tration of the examined drugs in which efficient QSAR (quantitative structure-activity relationship) andQSPR (quantitative structure-property relationship) models were generated using the calculated chro-matographic parameters (RM0and C0). The described models can provide a useful approach to predict MICand BBB penetration of newly synthesized FQs targeting to increase their activity against Gram-positiveorganisms and to minimize the associated CNS side effects.

The 2017 FDA safety review regarding the CNS (central nervous system) side effects associated withthe systemic use of fluoroquinolones antibacterials (FQs) was the key motivation to carry out this work.The main objective of this study is to investigate lipophilicity and retention parameters of some selectedfluoroquinolones antibacterials (FQs) namely; levofloxacin (LEV), ofloxacin (OFL), gatifloxacin (GAT), nor-floxacin (NOR), sparfloxacin (SPA), ciprofloxacin (CIP) and lomefloxacin (LOM) using salting-out thinlayer chromatography (SOTLC). Statistically significant correlations between the chromatographically-obtained retention parameters and experimental log P values were found and expressed as quantitativestructure retention relationship (QSRR) equations. Principal component analysis was carried out toexplain the variation between chromatographic and both experimental and computed lipophilicityparameters. In another aspect of this study, a comparison between the chromatographically-determinedretention parameters (for five of the drugs under study) obtained using SOTLC (current study) and rel-ative lipophilicity (RM0) determined using a previously reported RP (reversed-phase)-TLC method wascarried out. Statistically significant correlation between the two methods was found, although RM0valuesobtained using SOTLC was lower than those reported using RP-TLC. Multiple linear regression analysiswas performed to predict MIC (minimum inhibitory concentration) and blood brain barrier (BBB) pene-tration of the examined drugs in which efficient QSAR (quantitative structure-activity relationship) andQSPR (quantitative structure-property relationship) models were generated using the calculated chro-matographic parameters (RM0and C0). The described models can provide a useful approach to predict MICand BBB penetration of newly synthesized FQs targeting to increase their activity against Gram-positiveorganisms and to minimize the associated CNS side effects.

The 2017 FDA safety review regarding the CNS (central nervous system) side effects associated withthe systemic use of fluoroquinolones antibacterials (FQs) was the key motivation to carry out this work.The main objective of this study is to investigate lipophilicity and retention parameters of some selectedfluoroquinolones antibacterials (FQs) namely; levofloxacin (LEV), ofloxacin (OFL), gatifloxacin (GAT), nor-floxacin (NOR), sparfloxacin (SPA), ciprofloxacin (CIP) and lomefloxacin (LOM) using salting-out thinlayer chromatography (SOTLC). Statistically significant correlations between the chromatographically-obtained retention parameters and experimental log P values were found and expressed as quantitativestructure retention relationship (QSRR) equations. Principal component analysis was carried out toexplain the variation between chromatographic and both experimental and computed lipophilicityparameters. In another aspect of this study, a comparison between the chromatographically-determinedretention parameters (for five of the drugs under study) obtained using SOTLC (current study) and rel-ative lipophilicity (RM0) determined using a previously reported RP (reversed-phase)-TLC method wascarried out. Statistically significant correlation between the two methods was found, although RM0valuesobtained using SOTLC was lower than those reported using RP-TLC. Multiple linear regression analysiswas performed to predict MIC (minimum inhibitory concentration) and blood brain barrier (BBB) pene-tration of the examined drugs in which efficient QSAR (quantitative structure-activity relationship) andQSPR (quantitative structure-property relationship) models were generated using the calculated chro-matographic parameters (RM0and C0). The described models can provide a useful approach to predict MICand BBB penetration of newly synthesized FQs targeting to increase their activity against Gram-positiveorganisms and to minimize the associated CNS side effects.

A rapid, highly sensitive and roubst spectrofluorimetric method was developed for trace analysis of silymarin (SLM) in active pharmaceutical ingredient (API), pharmaceutical preparations and human plasma. The proposed method is based on reaction of SLM with a novel reagent; 3-amino-5-pyridin-3-yl-1,2,4-triazole (3-APT); in the presence of 0.04 M sodium hydroxide. The formed fluorescent product was formed within 5 min and was measured at 504 nm after excitation at 390 nm. All reaction parameters were optimized and the proposed method was validated according to ICH guidelines. The developed method was linearly correlated at the concentration range of 0.05–8 μg mL−1 with good correlation coefficient 0.9993, limit of detection 10.79 ng mL−1 and limit of quantitation 32.71 ng mL−1. The relative standard deviations %RSD values were 1.59–2.69% and 1.47–2.62% in case of intra- and inter-day precision, respectively. Computational molecular modeling and NMRspectroscopy were used to identify the reaction mechanismbetween SLMand 3-APT. The proposed methodwas employed for determination of SLMin API or bulk material, pharmaceutical capsules and sachets. Further, the method was sensitive enough to be applied for analysis of the free (unconjugated) SLMflavonolignans in human plasma samples.

A rapid, highly sensitive and roubst spectrofluorimetric method was developed for trace analysis of silymarin (SLM) in active pharmaceutical ingredient (API), pharmaceutical preparations and human plasma. The proposed method is based on reaction of SLM with a novel reagent; 3-amino-5-pyridin-3-yl-1,2,4-triazole (3-APT); in the presence of 0.04 M sodium hydroxide. The formed fluorescent product was formed within 5 min and was measured at 504 nm after excitation at 390 nm. All reaction parameters were optimized and the proposed method was validated according to ICH guidelines. The developed method was linearly correlated at the concentration range of 0.05–8 μg mL−1 with good correlation coefficient 0.9993, limit of detection 10.79 ng mL−1 and limit of quantitation 32.71 ng mL−1. The relative standard deviations %RSD values were 1.59–2.69% and 1.47–2.62% in case of intra- and inter-day precision, respectively. Computational molecular modeling and NMRspectroscopy were used to identify the reaction mechanismbetween SLMand 3-APT. The proposed methodwas employed for determination of SLMin API or bulk material, pharmaceutical capsules and sachets. Further, the method was sensitive enough to be applied for analysis of the free (unconjugated) SLMflavonolignans in human plasma samples.

Microwave reactors with on-line controlled reaction conditions have been recently innovated to improve reaction kinetics and reproducibility. Herein, a modern microwave reactor was dedicated to develop a new, sensitive and reproducible approach for trace analysis of budesonide (BUD) in human plasma. The method was based on fast microwave reaction of BUD with dansyl hydrazine (DNS-HZ) reagent under controlled conditions coupled with high-performance liquid chromatography (HPLC)-fluorescence detection. The microwave irradiation and dansylation conditions were optimized for the best sensitivity and selectivity. The controlled microwave derivatization reaction (CMDR) decreased the reaction time, amplified the reaction yield and enhanced product purities by reducing the unwanted side reactions. The chromatographic separation was attained by isocratic elution on reversed phase column via a mobile phase consisted of methanol and phosphate buffer (10 mM, pH 7.0) at ratio 80:20 (v/v). The fluorescence detector was set at 500 nm after excitation at 330 nm. Betamethasone dipropionate (BDP) was used as an internal standard. CMDR-HPLC method validation was performed in agreement with bioanalytical method validation guidelines by the US food and drug administration (US-FDA). The obtained linearity range was 0.2e100 ngmL1 with correlation coefficient 0.9991 and the lower limit of quantitation (LLOQ) in human plasma was 0.21 ngmL1. The developed CMDR -HPLC method was applied successfully for assessment of plasma levels of BUD in allergic rhinitis patients after intranasal administration of the micronized BUD.

Microwave reactors with on-line controlled reaction conditions have been recently innovated to improve reaction kinetics and reproducibility. Herein, a modern microwave reactor was dedicated to develop a new, sensitive and reproducible approach for trace analysis of budesonide (BUD) in human plasma. The method was based on fast microwave reaction of BUD with dansyl hydrazine (DNS-HZ) reagent under controlled conditions coupled with high-performance liquid chromatography (HPLC)-fluorescence detection. The microwave irradiation and dansylation conditions were optimized for the best sensitivity and selectivity. The controlled microwave derivatization reaction (CMDR) decreased the reaction time, amplified the reaction yield and enhanced product purities by reducing the unwanted side reactions. The chromatographic separation was attained by isocratic elution on reversed phase column via a mobile phase consisted of methanol and phosphate buffer (10 mM, pH 7.0) at ratio 80:20 (v/v). The fluorescence detector was set at 500 nm after excitation at 330 nm. Betamethasone dipropionate (BDP) was used as an internal standard. CMDR-HPLC method validation was performed in agreement with bioanalytical method validation guidelines by the US food and drug administration (US-FDA). The obtained linearity range was 0.2e100 ngmL1 with correlation coefficient 0.9991 and the lower limit of quantitation (LLOQ) in human plasma was 0.21 ngmL1. The developed CMDR -HPLC method was applied successfully for assessment of plasma levels of BUD in allergic rhinitis patients after intranasal administration of the micronized BUD.

Two new carbasugar-type metabolites, (1S,2R,3R,4R,5R)-2,3,4-trihydroxy-5-methylcyclohexyl-2',5'-dihydroxybenzoate (1) and (1S,2S,3S,4R,5R)-4-[(2',5'-dihydroxybenzyl)oxy]-5-methylcyclohexane-1,2,3-triol (2), were isolated from the filamentous fungus Geosmithia langdonii isolated from cotton textiles from Assiut, Egypt. The structures of 1 and 2 were elucidated based on comprehensive 1D and 2D NMR and MS data. Compounds 1 and 2 showed antileishmanial activity against Leishmania donovani with IC50 values of 100 and 57 μM, respectively. The (1S,2R,3R,4R,5R) absolute configuration of carbasugar 1 was assigned via 2D NMR and experimental and calculated electronic circular dichroism (ECD) data. Similarly, the tentative structure of compound 2 was shown to possess a (1S,2S,3S,4R,5R) absolute configuration via comparing its experimental ECD data and the specific rotation with 1 as well as examining the energy-minimized 3D computational models of compounds 1 and 2.

Two new carbasugar-type metabolites, (1S,2R,3R,4R,5R)-2,3,4-trihydroxy-5-methylcyclohexyl-2',5'-dihydroxybenzoate (1) and (1S,2S,3S,4R,5R)-4-[(2',5'-dihydroxybenzyl)oxy]-5-methylcyclohexane-1,2,3-triol (2), were isolated from the filamentous fungus Geosmithia langdonii isolated from cotton textiles from Assiut, Egypt. The structures of 1 and 2 were elucidated based on comprehensive 1D and 2D NMR and MS data. Compounds 1 and 2 showed antileishmanial activity against Leishmania donovani with IC50 values of 100 and 57 μM, respectively. The (1S,2R,3R,4R,5R) absolute configuration of carbasugar 1 was assigned via 2D NMR and experimental and calculated electronic circular dichroism (ECD) data. Similarly, the tentative structure of compound 2 was shown to possess a (1S,2S,3S,4R,5R) absolute configuration via comparing its experimental ECD data and the specific rotation with 1 as well as examining the energy-minimized 3D computational models of compounds 1 and 2.